The depressant effects of exogenous opiates on control of breathing have always been of interest because of the widespread use and abuse of these drugs. The recent discoveries of the opiate receptor and endogenously generated opiates (endorphins) have rekindled further interest in exogenous opiates and provoked systematic studies into the possible functions that these endorphins may subserve. Since endorphins are morphine-like in many respects, we feel that understanding their functions could be most efficiently accomplished by focusing the search on specific situations where morphine-like control of breathing responses are known to be manifested. This proposal therefore concerns itself with investigations of possible endorphin mediation of 1) the blunted responses to chemical and neuromechanical stimuli during sleep, 2) the blunted responses to acute hypoxia during chronic hypoxia, 3) the ventilator responses to brain hypoxia, 4) the impaired flow-resistive load compensation induced by obstructive airway disease and general anesthesia, and 5) the impaired responses to hypercapnia manifested by some patients with chronic lung disease. At the same time, we propose to continue further investigation into the respiratory effects of acute and chronic administration into the respiratory effects of acute and chronic administration of exogenous opiate drugs specifically as they pertain to perception of respiratory stimuli and their interaction with sleep. This dual approach which includes studies in human subjects as well as animals will, we believe, improve our understanding of how opiates, both exogenous and endogenous, affect respiration, both in health and during disease.